Long-acting
antiretroviral formulations (LA-ART), currently in development, aim to achieve
monthly or quarterly ART dosing; this could improve health benefits of ART for HIV-infected
individuals who have difficulty maintaining daily adherence. We sought to
identify the clinical and economic circumstances under which differing clinical
roles of LA-ART might be cost-effective in the US.

Methods:

We
used a microsimulation model of HIV disease progression (CEPAC-US) to project
the impact of 3 potential roles of LA-ART (compared to daily ART only): 1)
initial therapy for all ART-naïve patients, 2) 2nd-line therapy for
those failing 1st-line, and 3) use for patients with multiple prior
failures on NNRTI- and PI-based regimens. Model outcomes include
quality-adjusted life-years (QALYs), lifetime cost, and incremental
cost-effectiveness ratio (ICER); strategies with ICER < $100,000/QALY are
designated “cost-effective”. We simulate a cohort with mean adherence
(medication possession ratio) of 89% (SD = 22%). Depending on adherence, HIV
RNA < 400c/mL at 48 weeks on daily ART ranges from 0 to 91%, and loss to
follow-up ranges from 41 to 4/100PY. We assume LA-ART's efficacy is 91% regardless
of adherence to daily ART, and that LA-ART costs $60,000/patient-year (vs.
$28,000 for daily PI-based regimens). In sensitivity analysis, we vary LA-ART's
cost, efficacy, and quality of life (QOL) impact (due to benefits of reduced
pill burden or detrimental side effects).

Results:

In
the base case, LA-ART increases overall life expectancy (LE) compared to daily
ART by 0.5-0.6 years, and LE of patients with the lowest adherence by 2.3-3.0
years, depending on clinical role; only LA-ART for patients with multiple
failures is cost-effective ($86,000/QALY, Table). With a cost of $30,000/year
and a favorable QOL impact, 2nd-line LA-ART is cost-effective
($94,000/QALY); varying efficacy of LA-ART has minimal impact on
cost-effectiveness results.

Conclusion:

LA-ART could improve survival of US HIV
patients, especially those with barriers to adherence and poor outcomes on
daily ART. With a high cost, it will be a good value for use in patients with
multiple prior failures; a cost close to current regimens combined with
demonstrable QOL benefit would support broader use.